The disturbance of circadian rhythms and desynchronosis encountered by jet travelers, shift workers, persons on unconventional sleep-wake schedules and in aerospace operations, affect human physical performance as well as health. A number of treatments have been tested or suggested to alleviate the deleterious symptomatology associated with internal rhythm disturbances. However, many of the drugs which have been tested or utilized as experimental chronobiotics are inappropriate for operational use due to their high toxicity, negative side effects or long lasting action. The objective of the current proposal is to elucidate the neurochemical mechanisms of the beneficial effect of drugs which have been reported to be useful in facilitating readaptation following phase shifts, in an attempt to find the most effective and safe way to facilitate readaptation to phase shifts. To achieve this goal, the effects of chronobiotic drugs on the circadian rhythm of levels of norepinephrine, dopamine, serotonin, melantonin and endogenous opioids will be studied in specific rat brain regions and pineal gland. Caffeine, theophylline, ethanol and melatonin will be evaluated in rats kept under different light regimens. The rat is used as the experimental animal because it is a well established model in chronobiological research and the rat stimulates man in its directional asymmetry in response to phase shift. A better understanding of the role of neurotransmitters and neuromodulators in phase shifts and phase shift readaptation will contribute in finding the most effective and safest way to facilitate readaptation following desynchronosis.